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GABAA receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption

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Abstract

Rationale

The dorsal raphé nucleus (DRN), the origin for serotonin (5-HT) in forebrain areas, has been implicated in the neural control of escalated aggression. Gamma aminobutyric acid type-A (GABAA) and type-B (GABAB) receptors are expressed in the DRN and modulate 5-HT neuronal activity, and both play a role in the behavioral effect of alcohol.

Objective

The purpose of this study is to examine the interaction between drugs acting on GABA receptors in the DRN and alcohol in their effects on aggressive behaviors.

Method

Male CFW mice, housed with a female, were trained to self-administer ethanol (1.0 g/kg) or water via an operant conditioning panel in their home cage. Immediately after they drank either ethanol or water, the animals were microinfused with a GABAergic drug into the DRN, and their aggressive behaviors were assessed 10 min later. Muscimol (0.006 nmol), a GABAA receptor agonist, escalated alcohol-heightened aggression but had no effect in the absence of ethanol. This effect of muscimol was prominent in the animals that showed alcohol-heightened aggression, but not the animals that reduced or did not change aggressive behavior after ethanol infusion compared to water. On the other hand, the GABAB agonist baclofen (0.06 nmol) increased aggressive behavior similarly in both water and ethanol conditions. Antagonists of the GABAA and GABAB receptors, bicuculline (0.006 nmol) and phaclofen (0.3 nmol) respectively, did not suppress heightened-aggressive behavior induced by ethanol self-administration.

Conclusion

GABAA receptors in the DRN are one of the neurobiological targets of alcohol-heightened aggression. Activation of the GABAB receptors in the DRN also produced escalated aggression, but that is independent of the effect of alcohol.

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Acknowledgements

This research was supported by NIAAA grant AA13983.

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA

    Aki Takahashi, Carolyn Kwa, Joseph F. DeBold & Klaus A. Miczek

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  1. Aki Takahashi
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  2. Carolyn Kwa
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  3. Joseph F. DeBold
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  4. Klaus A. Miczek
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Correspondence to Klaus A. Miczek.

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Supplementary Table 1

Frequency of attack bites in animals that received microinfusion outside the DRN target site (DOC 38 kb)

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Takahashi, A., Kwa, C., DeBold, J.F. et al. GABAA receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption. Psychopharmacology 211, 467–477 (2010). https://doi.org/10.1007/s00213-010-1920-x

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